Association of single nucleotide polymorphisms of <i>MTHFR, TCN2, RNF213</i> with susceptibility to hypertension and blood pressure

Liu, Shan; Liu, Mengwei; Li, Qian; Liu, Xiuping; Wang, Yue; Mambiya, Michael; Zhang, Kaili; Yang, Luping; Zhang, Qian; Shang, Mengmeng; Zeng, Fanxin; Nie, Fangfang; Liu, Wanyang

doi:10.1042/bsr20191454

Cited by 17 publications

(9 citation statements)

References 54 publications

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“…In addition, MMD is also frequently accompanied with hypertension (17). A possible reason for this is that changes in RNF213 expression can result in increased blood pressure, which aggravates RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow-derived mesenchymal stem cells and is involved in the onset of Moyamoya disease intracranial hemodynamic disorders further and induce the formation of 'smoky' blood vessels (18,19). A homozygous variant of RNF213 is considered to be the most pathogenic and was found to be significantly associated with severe manifestations of MMD (20).…”

Section: Introductionmentioning

confidence: 99%

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow‑derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

et al. 2021

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Moyamoya disease (MMD) is a chronic and progressive cerebrovascular occlusion disease, the precise etiology of which is poorly understood. Ring finger protein 213 (RNF213) has been previously identified as a susceptibility gene that serves an important role in angiogenesis, where it has been shown to be closely associated with the onset of MMD. Patients with MMD exhibit increased expression levels of various pro-inflammatory molecules and angiogenic factors. Under certain conditions, bone marrow mesenchymal stem cells (BMSCs) have the ability to differentiate to form neuron-like and microglia-like cells. In the present study, a total of 40 MMD patients and 40 healthy individuals were enrolled. ELISA assays revealed that the expression of serum vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) were higher than that in healthy controls. Furthermore, rat BMSCs (rBMSCs) were isolated and cultured using the whole bone marrow adherence method, which were then phenotyped using flow cytometry. Osteogenic and adipogenic differentiation were determined by using Alizarin red and oil red O staining, respectively. RNF213 was knocked-down using a lentivirus-mediated short hairpin RNA system in passage three rBMSCs, and successful transfection of the RNF213 was confirmed by RT-qPCR and fluorescence imaging. The expression levels of VEGF and TGF-β1 in these rBMSCs were measured on days 7 and 14, respectively. The results demonstrated that RNF213 knockdown upregulated TGF-β1 at both protein and mRNA levels, but did not exert any effect on VEGF gene expression. In conclusion, these findings suggested that that RNF213 knockdown may contribute to aberrant TGF-β1 expression via a pathway that remains to be unidentified, indicating that quantitative changes in RNF213 gene expression may serve an important role in the pathogenesis of MMD.

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Section: Introductionmentioning

confidence: 99%

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow‑derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

et al. 2021

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“…For instance, the T allele was associated with a higher risk of hypertension in Taiwanese ( 48 ), Chinese ( 47 , 50 , 77 ), Indians ( 78 ), and Australian Caucasians ( 52 ), and the TT genotype in Moroccans ( 51 ). Nonetheless, the variant was not significantly associated with hypertension in Algerians ( 79 ), South Africans ( 80 ), Chinese ( 54 , 81 ), Danish ( 53 ), Caucasians ( 55 ), Japanese ( 56 ), Black Africans ( 76 ), Latinos ( 76 ), Sri Lankans ( 76 ), and Indians ( 76 ). We believe that the conflicting results between our study and those previously reported could, in part, be due to differences in ethnicities, sample sizes, and study designs.…”

Section: Discussionmentioning

confidence: 95%

Susceptibility to hypertension based on MTHFR rs1801133 single nucleotide polymorphism and MTHFR promoter methylation

Chiu,

Chang,

Tantoh

et al. 2023

Front. Cardiovasc. Med.

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BackgroundThe aetio-pathologenesis of hypertension is multifactorial, encompassing genetic, epigenetic, and environmental factors. The combined effect of genetic and epigenetic changes on hypertension is not known. We evaluated the independent and interactive association of MTHFR rs1801133 single nucleotide polymorphism (SNP) and MTHFR promoter methylation with hypertension among Taiwanese adults.MethodsWe retrieved data including, MTHFR promoter methylation, MTHFR rs1801133 genotypes (CC, CT, and TT), basic demography, personal lifestyle habits, and disease history of 1,238 individuals from the Taiwan Biobank (TWB).ResultsThe distributions of hypertension and MTHFR promoter methylation quartiles (β < 0.1338, 0.1338 ≤ β < 0.1385, 0.1385 ≤ β < 0.1423, and β ≥ 0.1423 corresponding to <Q1, Q1–Q2, Q2–Q3, and ≥Q3) among individuals with the rs1801133 genotypes (CC, CT, and TT) were significantly different (P < 0.05). The risk of hypertension was significantly higher among individuals with the TT genotype compared to the reference genotype (CC): odds ratio (OR); 95% confidence interval (CI) = 2.718; 1.503–4.914. The trend of the association of the CT and TT genotypes with hypertension was dose-dependent (P-trend = 0.0041). MTHFR promoter methylation (lower quartiles compared to ≥Q3) was not significantly associated with hypertension. However, its interaction with MTHFR rs1801133 was significant (P = 0.0323). After stratification by rs1801133 genotypes, lower MTHFR promoter methylation quartiles (<Q1, Q1–Q2, Q2–Q3) compared to ≥Q3 were significantly associated with a higher risk of hypertension among individuals carrying the CC genotype: ORs (95% CIs) = 3.225 (1.140–9.124), 4.177 (1.424–12.247), and 8.645 (2.513–29.739) for Q2–Q3, Q1–Q2, and <Q1, respectively. The trend test was significant (P-trend = 0.0009).ConclusionIndependently, rs1801133 TT was associated with a higher risk of hypertension, but methylation was not. Based on genotypes, lower methylation was dose-dependently associated with a higher risk of hypertension in individuals with the CC genotype. Our findings suggest that MTHFR rs1801133 and MTHFR promoter methylation could jointly influence hypertension susceptibility.

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“…Studies about some populations in the three northeastern provinces of China have found that polymorphisms in the MTHFR genes A1298C and C677T are not significantly associated with hypertension ( Liu et al, 2019 ). In this case-control study of oil workers in Karamay, Xinjiang, adjusting for confounding factors, mutant genes at the A1298C polymorphism and the C677T polymorphism of the MTHFR gene were found to be susceptible genotypes for hypertension, which is consistent with the findings of and Alghasham et al (2012) .…”

Section: Discussionmentioning

confidence: 99%

Effect of interaction between occupational stress and polymorphisms of MTHFR gene and SELE gene on hypertension

Yang

Qiu

Abudoubari

et al. 2022

PeerJ

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Background Gene-environment interaction is related to the prevalence of hypertension, but the impact of genetic polymorphisms on hypertension may vary due to different geography and population. Objective To explore the impact of the interaction among occupational stress and MTHFR gene and SELE gene polymorphism on the prevalence of hypertension in Xinjiang oil workers. Methods A case-control study was conducted on 310 oil workers. In an oilfield base in Karamay City, Xinjiang, 155 hypertensive patients aged 18~60 years old with more than one year of service were selected as the case group, and 155 oil workers without hypertension were selected as the control group according to the 1:1 matching principle (matching conditions: the gender and shift were the same. The age is around 2 years old). The Occupational Stress Scale was used to evaluate the degree of occupational stress, PCR technique was used to detect MTHFR and SELE gene polymorphism, Logistic regression analysis was used to analyze the effects of gene and occupational stress on hypertension, and gene-gene and gene-environment interactions were analyzed by generalized multi-factor dimension reduction method. Results The G98T polymorphism of SELE gene (χ2 = 6.776, P = 0.034), the C677T (χ2 = 7.130, P = 0.028) and A1298C (χ2 = 12.036, P = 0.002) loci of MTHFR gene and the degree of occupational stress (χ2 = 11.921, P = 0.003) were significantly different between the case group and the control group. The genotypes GT at the G98T polymorphism of the SELE gene (OR = 2.151, 95% CI [1.227–3.375]), and the dominant model (AC/CC vs AA, OR = 1.925, 95% CI [1.613–3.816]); AC and CC at the A1298C polymorphism of the MTHFR gene (ORAC = 1.917, 95% CI [1.064–3.453]; ORCC = 2.233, 95% CI [1.082–4.609]), the additive model (CC vs AA, OR = 2.497, 95% CI [1.277–4.883]) and the dominant model (AC/CC vs AA, OR = 2.012, 95% CI [1.200–3.373]); at the C677T polymorphism of the MTHFR gene CT and TT (ORCT = 1.913, 95% CI [1.085–3.375]; ORTT = 3.117, 95% CI [1.430–6.795]), the additive model (CC vs AA, OR = 1.913, 95% CI [1.085–3.375]) and the dominant model (AC/CC vs AA, OR = 2.012, 95% CI [1.200–3.373]), which could increase hypertension risk (P < 0.05). The gene-gene interaction showed that there was a positive interaction between the A1298C and C677T sites of the MTHFR gene, and the gene-occupational stress interaction showed that there was a positive interaction between the A1298C and C677T sites of the MTHFR gene and the occupational stress. Conclusion The interaction of gene mutation and occupational stress in Xinjiang oil workers maybe increase the risk of hypertension.

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Association of single nucleotide polymorphisms of MTHFR, TCN2, RNF213 with susceptibility to hypertension and blood pressure

Cited by 17 publications

References 54 publications

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow‑derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow‑derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

Susceptibility to hypertension based on MTHFR rs1801133 single nucleotide polymorphism and MTHFR promoter methylation

Effect of interaction between occupational stress and polymorphisms of MTHFR gene and SELE gene on hypertension

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